Infection with the ubiquitous gamma-herpesvirus Epstein-Barr virus (EBV) is implicated in the pathogenesis of several cancers, particularly in immunocompromised individuals. EBV-associated non-Hodgkin lymphoma (NHL) develops frequently in HIV+ individuals and is an AIDS-defining illness, and limited data from studies in developed countries suggest that loss of EBV-specific T cell responses is associated with the progression to NHL in this setting. The role of EBV in progression to AIDS-defining NHL in resource-limited settings such as sub-Saharan Africa, where the natural history of EBV infection is quite distinct from that observed in developed countries, is poorly defined. The studies proposed in this project will focus on EBV infection and EBV immunity in the natural history of HIV-associated NHL in Uganda. We hypothesize that NHL in H1V+ individuals in Uganda represents an EBV-driven lymphoproliferation that occurs in the setting of defective T cell immunity to EBV. The specific aims of this project are: (1) To identify pathologic, virologic, and immunologic characteristics at the time of diagnosis that correlate with survival in H1V+ individuals who present to the Uganda Cancer Institute with NHL. (2) To identify characteristics of the global and EBV-specific CD4+ and CD8+ T cell repertoire among H1V+ patients newly diagnosed with NHL, and to determine if survival for one year after diagnosis is associated with enhancement of EBV-specific T cell immunity and improvement in the global CD4+ and CD8+ T cell repertoire. It is anticipated that the results of this project will provide the rationale for development of interventions to stimulate EBV-specific immunity in H1V+ individuals presenting with NHL in Uganda and improve survival.